d-Asb11 is an essential mediator of canonical Delta-Notch signalling

Sander H. Diks, Maria A. Sartori da Silva, Jan-Luuk Hillebrands, Robert J. Bink, Henri H. Versteeg, Carina van Rooijen, Anke Brouwers, Ajay B. Chitnis, Maikel P. Peppelenbosch*, Danica Zivkovic

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

20 Citaten (Scopus)

Samenvatting

In canonical Delta-Notch signalling, expression of Delta activates Notch in neighbouring cells, leading to of Delta in these cells(1). This process of lateral inhibition results in selection of either Delta-signalling cells or Notch-signalling cells. Here we show that d-Asb11 is an important mediator of this lateral inhibition. In zebrafish embryos, morpholino oligonucleotide (MO)-mediated knockdown of d-Asb11 caused repression of specific Delta-Notch elements and their transcriptional targets, whereas these were induced when d-Asb11 was misexpressed. d-Asb11 also activated legitimate Notch reporters cell-non-autonomously in vitro and in vivo when co-expressed with a Notch reporter. However, it repressed Notch reporters when expressed in Delta-expressing cells. Consistent with these results, d-Asb11 was able to specifically ubiquitylate and degrade DeltaA both in vitro and in vivo. We conclude that d-Asb11 is a component in the regulation of Delta-Notch signalling, important in fine-tuning the lateral inhibition gradients between DeltaA and Notch through a cell non-autonomous mechanism.

Originele taal-2English
Pagina's (van-tot)1190-1198
Aantal pagina's9
TijdschriftNature Cell Biology
Volume10
Nummer van het tijdschrift10
DOI's
StatusPublished - okt.-2008

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